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用于结直肠癌成像的锌酞菁-抗癌胚抗原生物共轭物的合成与生物学研究

Synthesis and biological investigations of a ZnPc-antiCEA bioconjugate for imaging of colorectal cancer.

作者信息

Sehgal Inder, Li Hairong, Ongarora Benson, Devillier Daniel, Vicente M Graça H

机构信息

Department of Comparative Biomedical Sciences, School of Veterinary Medicine, Louisiana State University, Baton Rouge, LA 70803, USA.

Department of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USA.

出版信息

J Porphyr Phthalocyanines. 2013 Jan 1;17(1-2):150-156. doi: 10.1142/S108842461250143X.

Abstract

Two zinc(II) phthalocyanines (ZnPcs) were conjugated with a monoclonal antibody (MAb) directed against carcinoembryonic antigen (CEA), using an activated carboxylic acid on the ZnPcs. The bioconjugate with the highest ZnPc/MAb ratio of 3 was investigated for its ability to target and fluorescently label human colorectal HT-29 cells. The ZnPc-CEA MAb was observed to efficiently target HT-29 cells, about 37 times more than unconjugated ZnPc. Furthermore, in the presence of a 4-fold excess of unlabelled anti-CEA antibody, the fluorescence signal of was reduced by ~90% showing that the targeting is CEA-mediated. These studies further confirm the high specificity of Pc-antibody conjugates for antigens over-expressed on tumor cells and warrant further investigations of these immunoconjugates and their derivatives for imaging of colorectal cancer.

摘要

利用酞菁锌(ZnPcs)上的活性羧酸,将两种锌(II)酞菁与一种针对癌胚抗原(CEA)的单克隆抗体(MAb)偶联。研究了锌酞菁/单克隆抗体比例最高为3的生物偶联物靶向和荧光标记人结肠HT-29细胞的能力。观察到锌酞菁-CEA单克隆抗体能有效靶向HT-29细胞,其效率约为未偶联锌酞菁的37倍。此外,在存在4倍过量未标记抗CEA抗体的情况下,荧光信号降低了约90%,表明这种靶向作用是由CEA介导的。这些研究进一步证实了酞菁-抗体偶联物对肿瘤细胞上过度表达的抗原具有高度特异性,并值得对这些免疫偶联物及其衍生物进行进一步研究,用于结直肠癌成像。

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